Polyethoxylated castor oil is a surfactant commonly used in a number of products for its emulsifying properties. In many contexts, it is a necessary agent to solubilize certain active agents, especially active agents which are only slightly or sparingly soluble in water. While the polyethoxylated castor oil is a suitable solubilizer for many agents, in a number of situations, those agents exhibit unacceptable degradation when the polyethoxylated castor oil is present.
One formulation containing polyethoxylated castor oil in which the active agent is degraded in the presence of polyethoxylated castor oil to a greater degree than in its absence is shown in U.S. Pat. No. 4,960,799, issued to Nagy on Oct. 2, 1990. In the invention there, the problem was stated as being solved by incorporation of a stabilizer, in particular, ethylene diamine tetraacetic acid (EDTA). EDTA is used in many aqueous pharmaceutical purposes, including as a sequesterant for multivalent ions.
In another pharmaceutical formulation, polyethoxylated castor oil is used as a solubilizer for a non-aqueous concentrate formulation of paclitaxel, which is, in use, diluted with either aqueous carrier for use as an infusion. Formulations prepared according to the label contents of this product using standard, commercially available, polyethoxylated castor oil (CREMOPHOR EL.RTM. available from BASF) and natural paclitaxel show fairly rapid degradation of the active moiety.
The currently U.S. marketed paclitaxel formulation (available from Bristol-Myers Squibb) does not show as rapid a degradation pattern as that observed with the formulations prepared above, but the Bristol-Myers Squibb product is formulated from semisyntheic active agent. Analysis of the Bristol-Myers Squibb product also revealed a reduced cation content relative to that of the formulation prepared above.